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Biomedical subjects

H Bertz

Publications and source records attributed to H Bertz.

At least 19 recordsLinked to original sources

Human metapneumovirus infection in a hematopoietic stem cell transplant recipient with relapsed multiple myeloma and rapidly progressing lung cancer.

Human metapneumovirus (HMPV) was isolated from a 63-year-old multiple myeloma patient who had undergone hematopoietic stem cell transplantation and who presented with lower respiratory tract infection several weeks prior to the diagnosis of lung cancer. The isolate was phylogenetically and biologically characterized and compared to HMPV prototypes and recent pediatric isolates. Remarkably, it belonged to the novel genomic subgroup A2b.

Animals↗

Surveillance of nosocomial sepsis and pneumonia in patients with a bone marrow or peripheral blood stem cell transplant: a multicenter project.

BACKGROUND: For surveillance of nosocomial bloodstream infections (BSIs) and pneumonia during neutropenia in adult patients who have undergone bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), a multicenter study--the Hospital Infection Surveillance System for Patients with Hematologic/Oncologic Malignancies (ONKO-KISS)--was initiated in Germany in 2000. METHODS: Nosocomial infections were identified in neutropenic patients by means of Centers for Disease Control and Prevention definitions for laboratory-confirmed BSI and modified criteria for pneumonia. RESULTS: During the first 38-month period of the study (i.e., through December 2003), a total of 1899 patients associated with 28,273 neutropenic days were investigated. Of these, 1173 (62%) had undergone allogeneic and 726 (38%) had undergone autologous BMT or PBSCT. The mean duration of neutropenia was 14.9 days (9.6 and 18.1 days after autologous and allogeneic transplantation, respectively). Overall, 395 BSIs and 168 cases of pneumonia were identified. The pooled mean site-specific incidence density per 1000 neutropenic days was 14.0 for BSI (12.4 and 18.9 for the allogeneic and autologous transplantation groups, respectively) and 5.9 for pneumonia (6.1 and 5.6 in the allogeneic and autologous transplantation groups, respectively). After allogeneic transplantation, 22.4 BSIs per 100 patients and 11.0 cases of pneumonia per 100 patients occurred, whereas 18.2 BSIs per 100 patients and 5.4 cases of pneumonia per 100 patients occurred after autologous transplantation. The majority (57%) of pathogens associated with BSI were coagulase-negative staphylococci. CONCLUSIONS: The ongoing ONKO-KISS project provides unprecedented reference data about the incidence of pneumonia and sepsis among BMT recipients and PBSCT recipients in Germany. These data will be used for further evaluation of the impact of hygiene measures and therapeutic regimens for these patients.

Adolescent↗

Breakthrough invasive infection due to Debaryomyces hansenii (teleomorph Candida famata) and Scopulariopsis brevicaulis in a stem cell transplant patient receiving liposomal amphotericin B and caspofungin for suspected aspergillosis.

An allogeneic stem cell transplant recipient developed pulmonary infiltrates and Aspergillus antigenemia during prophylactic low-dose liposomal amphotericin B. No response to therapy was observed after increasing the dose of liposomal amphotericin B and addition of caspofungin, and breakthrough candidemia developed. Therapy switch to voriconazole did not prevent the development of lethal septic shock. Shortly before death, Scopulariopsis brevicaulis was cultured from bronchial secretions, and positive blood cultures demonstrated persistent candidemia due to Debaryomyces hansenii, teleomorph of Candida famata.

Aged↗

Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation.

Both conventional chimerism analysis (CCA) and lineage-specific chimerism analysis (LCA) have potential pitfalls as diagnostic means for the detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). Therefore, the present study examines the results of both methods in order to determine how predictive consecutive evaluations were, with respect to the risk that the patient would relapse during post-transplant follow-up and with respect to responsiveness to immunomodulatory treatment. A total of 168 individuals with acute myeloid leukemia (AML) (n = 137) and myelo dysplastic syndrome (n = 31) were investigated with CCA and LCA at mean intervals of 24 days (range: 11-116). The median follow-up after myeloablative aHCT was 22 months (range: 4-49). Of 168 patients, 65 experienced a clinical relapse after aHCT. CCA and LCA were comparatively sensitive and specific for relapse at the intervals of chimerism testing employed in this study. Of 32 patients, 10 who were offered donor lymphocyte infusions (DLI) treatment for increasing (n = 29) or stable (n = 3) mixed chimerism (MC) achieved at least transitory CC. The observation that all patients with increasing MC relapsed despite DLI treatment (54%) or withdrawal of immune suppression (24%) indicates that novel strategies to deal with rapidly evolving relapse in AML patients, such as shortening of chimerism monitoring intervals, need to be evaluated.

Cell Lineage↗

Late cytomegalovirus polyradiculopathy following haploidentical CD34+-selected hematopoietic stem cell transplantation.

A 55-year-old man with acute myeloid leukemia in second relapse presented 4 months after haploidentical CD34+-selected hematopoietic stem cell transplantation (HSCT) with symmetric, progressive neurological deficits of the lower extremities. Although there was no molecular evidence for drug resistance in the cerebral-spinal fluid, antiviral combination therapy failed to control the rapidly progressing CMV polyradiculopathy (PRP) and encephalitis, which were confirmed by autopsy studies. Late CMV PRP as an unusual manifestation of CMV disease should be kept in mind in patients with suggestive neurological symptoms after HSCT.

Acute Disease↗

Evidence for a graft-versus-mast-cell effect after allogeneic bone marrow transplantation.

Mast cell leukemia (MCL) is a rare form of aggressive mastocytosis with a reported median survival below 6 months. Casuistic reports suggest the effectiveness of allogeneic bone marrow transplantation (BMT) for MCL. However, these reports lack clear evidence for a graft-versus-mast-cell (GvMC) effect. We prospectively investigated the GvMC at different time points after allogeneic BMT and donor-lymphocyte infusions (DLI). Samples were gathered from a patient with MCL treated with allogeneic BMT from an unrelated HLA identical donor. Parameters for detection of a GvMC effect included flow cytometrical analysis of mast cell (MC) populations in peripheral blood and BM, BM smear and histology, chimerism analysis of flow cytometrically sorted BM CD117+/CD34- MC and testing for anti-mast cell reactivity of donor lymphocytes by interferon (IFN)-gamma ELISPOT. DLIs reduced MC from 5 to 0.5%. MC chimerism analysis demonstrated a complete recipient genotype after BMT, suggesting that the persistent mastocytosis was part of residual neoplastic disease. At 3.7 years after BMT, there is some evidence for relapse. In summary, BMT and DLIs attenuated the mastocytosis from an aggressive to an indolent form and may have improved the patients' prognosis. The in vitro data of our study indicate for the first time the existence of a GvMC effect.

Adult↗

Donor lymphocyte infusions for multiple myeloma: clinical results and novel perspectives.

Donor lymphocyte infusions (DLIs) provide effective therapy for patients with various hematological malignancies who have relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). In patients with multiple myeloma (MM), DLIs can induce response rates of 40-52%. DLIs were employed as treatment for MM relapse or as prophylaxis for relapse in MM patients undergoing allo-HSCT. The clinically most relevant treatment-related morbidity with DLIs is the occurrence of graft-versus-host disease (GVHD). Secondly, graft failure and the immune escape of extramedullary plasmocytoma have been reported. The fact that previous clinical reports have documented graft-versus-myeloma (GVM) activity without GVHD suggests that at least two distinct immunocompetent cell populations mediating GVHD and/or GVM may exist. Further characterization of the effector cells such as T cells and/or NK cells and their targets may help to clarify the immune response that mediates the GVM effect. This review considers the results of clinical approaches with DLI for MM, with emphasis on strategies to prevent GVHD while preserving the GVM effect. Furthermore, currently investigated molecular antigenic targets for the GVM effect such as MM-specific idiotypic determinant of immunoglobulin variable regions, several PRAME epitopes and antigenic structures encoded by cancer germline-specific genes as candidates for immunotherapy trials are discussed.

Female↗

Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome.

Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto- (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, beta2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto- and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT.

Adult↗

Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index.

BACKGROUND: To evaluate the long-term benefit from high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT), as part of the initial treatment for patients with chemosensitive, high-grade B non-Hodgkin's lymphoma (hg B-NHL), stratified according to the age-adjusted International Prognostic Index (aaIPI). PATIENTS AND METHODS: Eligible patients were 33 consecutive hg B-NHL patients responding to first-line chemotherapy and fulfilling at least one of the following criteria: stage III or IV, bulky disease, elevated lactate dehydrogenase or failure to achieve complete remission (CR). Twenty-two of 33 patients (67%) had two or three risk factors with respect to the aaIPI. All patients received HDCT with ASCT after a minimum of 6 weeks of VACOP-B standard therapy and VIP-E for mobilization. RESULTS: After ASCT, 31 patients (94%) achieved CR. No treatment-related death occurred. The cumulative incidence of relapse at a medium follow-up of 10 years is 16% for 31 of 33 patients achieving CR. Twenty-five of 33 patients are in sustained CR with a disease-free survival of 76% [95% confidence interval (CI) 67% to 86%]. The overall survival at a median follow-up of 122 months (range 86-148) is 79% (95% CI 68% to 89%). CONCLUSIONS: The results suggest that up-front HDCT with ASCT may improve long-term outcome in high-risk patients with chemotherapy-sensitive hg B-NHL when compared to historic populations treated solely with dose-intense chemotherapy. We observed that long-term survival of high-risk (two to three risk factors) patients is comparable to low-risk (zero to one risk factor) patients after HDCT and ASCT with a low incidence of late relapse.

Adult↗

Treatment with granulocyte colony-stimulating factor increases interleukin-1 receptor antagonist levels during engraftment following allogeneic stem-cell transplantation.

BACKGROUND: The effect of treatment with granulocyte colony-stimulating factor (G-CSF) on interleukin-1 receptor antagonist (IL-1ra) plasma concentrations as well as the role of IL-1ra on leucocyte recovery and parameters of infection within the first 30 days after haematopietic stem-cell transplantation (HSCT) are not well known. MATERIAL AND METHODS: Twenty-seven patients undergoing myeloablative therapy followed by allogeneic SCT for various haematological disorders were either treated with (n = 18) or without (n = 9) G-CSF. IL-1ra plasma levels were serially determined by ELISA starting at day - 1 and continued until patients were engrafted. RESULTS: Patients receiving G-CSF had significantly shorter neutropenic periods and significantly lower mean C-reactive protein serum levels during the first 3 weeks succeeding bone marrow transplantation (BMT). Importantly, starting at day + 11 and paralleling the rise of peripheral blood leucocytes, increasing IL-1ra plasma concentrations were observed in both treatment groups. However, the magnitude of the IL-1ra surge was far greater in the G-CSF treatment group. Peak IL-1ra plasma level observed on day + 19 was 882.3 +/- 879.2 pg mL(-1) (mean +/- SD) in patients receiving G-CSF compared with 285.8 +/- 175.2 pg mL(-1) (mean +/- SD) in patients not receiving G-CSF (P = 0.0130). Furthermore, a direct correlation of IL-1ra with peripheral blood leucocytes was verified by the Spearman rank test (P = 0.0025). CONCLUSION: Granulocyte colony-stimulating factor-mediated acceleration of neutrophil recovery following myeloablative therapy correlated with increased IL-1ra plasma concentrations. Our data suggest that IL-1ra constitutes an intrinsic component of the anti-inflammatory and neutrophil differentiating efficacy of G-CSF and, thus, IL-1ra may be required for the in vivo activity of G-CSF.

Bone Marrow Transplantation↗

Relationship between psychosocial distress, treatment need and use of psychotherapeutic interventions within a psychosomatic liaison service in hematological oncology.

BACKGROUND: Psychosocial distress is common in patients with hematological malignancies in the acute phase of the disease. The aim of the study was to evaluate the treatment need and the realization of psychotherapeutic interventions of a routine psychosomatic liaison service delivery in hematological oncology. PATIENTS AND METHODS: 72 patients of the transplantation ward and of the general hematological oncological ward were consecutively included in the study. Assessments involved both self- and observer rating instruments. RESULTS: The need for psychotherapeutic treatment was 38 or 49%, depending on patients' or professional's view, respectively. 39% of the patients underwent psychotherapeutic treatment. But there was a great discrepancy between the treatment need estimated by observer and patients and the actual psychotherapeutic interventions. CONCLUSIONS: The utilization of psychotherapeutic interventions seems to be subject to a complex interaction between patient's need, 'objective' psychosocial distress and institutional conditions. The results highlight the importance of need for better identification of patients with psychosocial distress and better targeting of psychotherapeutic treatment.

Attitude to Health↗

Surveillance of nosocomial infections in adult recipients of allogeneic and autologous bone marrow and peripheral blood stem-cell transplantation.

To identify overall and site-specific rates of nosocomial infections (NIs) during the neutropenic, as compared to the non-neutropenic stage of treatment in adult recipients of allogeneic and autologous bone marrow transplantation (BMT) and peripheral blood stem-cell transplantation (PBSCT), a prospective, 54-month study was started at the Haematological Stem Cell Transplantation Unit of the University Hospital of Freiburg, Germany. NI types were identified using modified CDC definitions. A total of 351 patients (14 256 in-patient days, 5026 neutropenic days) were investigated (316/90% allogeneic, 35/10% autologous; BMT: 119 patients, PBSCT: 234 patients). The mean length of neutropenia was 14.3 days (range: 0-66). Antimicrobial prophylaxis for allogeneic transplantation consisted of ciprofloxacin, trimethoprim/sulpha-methoxazole, fluconazole, and metronidazole. In total, 239 NIs were identified in 169 patients (48.1%), and of these 171 (71.5%) occurred during neutropenia (34.0 NIs per 1000 days at risk). The main pathogens were coagulase-negative staphylococci (36.3%), Clostridium difficile (20.4%), and enterococci (10.0%). Site-specific incidence densities during neutropenia vs non-neutropenia were: 13.9 vs 1.6 bloodstream infections (all central line-associated), 11.9 vs 1.8 pneumonias, 3.0 vs 2.9 gastroenteritis, and 1.6 vs 0.3 urinary tract infections. The greatest number of NI in BMT and PBSCT recipients is acquired during neutropenia, and multicentre surveillance programmes should focus on this.

Adult↗

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation.

In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of >1.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-alpha antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.

Adult↗

ATG as part of the conditioning regimen reduces transplant-related mortality (TRM) and improves overall survival after unrelated stem cell transplantation in patients with chronic myelogenous leukemia (CML).

Matched unrelated donor transplants have an increased risk of severe graft-versus-host disease and transplant-related mortality (TRM). ATG has been introduced to decrease GvHD and to facilitate engraftment. We conducted a retrospective analysis of 333 patients with chronic myelogenous leukemia, who were treated with Fresenius ATG (n=145, average=90 mg/kg bw, range 40-90 mg/kg bw) or standard immunosuppression without ATG (n=188). Both groups were comparable regarding distribution of age, sex, HLA-matched vs mismatched donors. ATG Fresenius led to a faster leukocyte engraftment, decreased the incidence of acute GvHD and TRM (P=0.01 and P=0.03) and led to a significant better overall survival (70 vs 57%, P=0.03). We concluded that a prospective randomized study is needed to evaluate the definite role of ATG in hemopoietic stem cell transplantation.

Acute Disease↗

Allogeneic hematopoetic stem-cell transplantation for patients with relapsed or refractory lymphomas: comparison of high-dose conventional conditioning versus fludarabine-based reduced-intensity regimens.

BACKGROUND: Allogeneic hematopoetic stem-cell transplantation (alloHSCT) has curative potential for poor risk lymphoma patients due to the graft-versus-lymphoma effect. High non-relapse mortality with conventional high-dose conditioning indicates the necessity for less toxic transplant strategies. PATIENTS AND METHODS: Between 1992 and 1999, 25 patients [median age 37 (20-60) years] with relapsed or refractory non-Hodgkin's lymphoma (NHL, n = 20) or Hodgkin's disease (HD, n = 5) received an alloHSCT in our institution. Patients were grafted from HLA matched (17) or mismatched (2) related, or matched unrelated donors (MUD) (6). NHL histological subtypes were lymphoblastic (6), high grade B/T-cell lymphomas (5), follicular (3), mantle cell (2) and CLL, immunocytic, composite lymphoma and panniculitic T-NHL in one patient each. Patients had received a median of four (range three to six) different therapies before alloHSCT, and 10 patients had relapsed after high-dose chemotherapy and autologous (9) or allogeneic (1) HSCT. Remission status prior to allogeneic SCT was CR1 (1), CR2 (1), relapse (11), partial remission (5) or primary refractory induction failure (7). Conventional myeloablative conditioning (cc) regimens contained total body irradiation 12 Gy (5), busulfan 16 mg/kg (7) or BCNU/VP16 (1). Twelve patients received reduced-intensity conditioning (ric) regimens with fludarabine (FLU) plus alkylating agents. Graft-versus-host disease prophylaxis consisted of cyclosporin A +/- prednisone or methotrexate. Six patients also received anti-T-lymphocyte globulin. RESULTS: Twenty-four patients engrafted. Best response after alloHSCT was complete remission in 16 of all patients [64%: 95% confidence interval (CI) 44% to 84%] and in 16 of 22 evaluable patients (73%: 95% CI 53% to 93%), partial remission in three of 25 (12%), and no change in three of 25 (12%) patients. Early death prevented response evaluation in three of 25 patients. Non-relapse mortality was 54% (95% CI 15% to 78%) in patients after cc and 17% (95% CI 0% to 41%) after FLU-based ric (P = 0.03). Six patients died due to progressive disease or relapse. Four patients with HD died, three in complete remission due to non-relapse mortality and one with progressive disease. Eleven of 25 patients are alive with a median follow up of 618 days (range 383-2815), with an overall survival of 44% (95% CI 23% to 65%) at 1 year for all patients, while eight of 12 (67%: 95% CI 35% to 98%) patients are alive after ric compared with three of 13 (23%; 95% CI 0% to 50%) after cc (P <0.02). CONCLUSIONS: AlloHSCT induces high rates of complete remission in advanced lymphoma patients, even when the tumor had relapsed after autologous HSCT. It should be considered earlier as part of the therapeutic options in poor risk patients to avoid non-relapse mortality associated with extensive pretreatment. Our novel reduced conditioning regimens show promising results, especially in heavily pretreated patients, and improve survival after allogeneic transplantation.

Adult↗